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比较黎豆种子提取物与雌激素在 1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)诱导的 PD 小鼠模型中的神经保护潜力。

Comparison of the neuroprotective potential of Mucuna pruriens seed extract with estrogen in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mice model.

机构信息

Department of Biochemistry, Faculty of Science, Banaras Hindu University, Varanasi 221005, India.

Department of Medicinal Chemistry, Institute of Medical Science, Banaras Hindu University, Varanasi 221005, India.

出版信息

Neurochem Int. 2014 Jan;65:1-13. doi: 10.1016/j.neuint.2013.12.001. Epub 2013 Dec 11.

Abstract

Parkinson's disease (PD) is one of the most common neurodegenerative disease found in the aging population. Currently, many studies are being conducted to find a suitable and effective cure for PD, with an emphasis on the use of herbal plants. In Ayurveda, Mucuna pruriens (Mp), a leguminous plant, is used as an anti-inflammatory drug. In this study, the neuroprotective effect of an ethanolic extract of Mp seed is evaluated in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of PD and compared to estrogen, a well reported neuroprotective agent used for treating PD. Twenty-four Swiss albino mice were randomly divided into four groups: Control, MPTP, MPTP+Mp and MPTP+estrogen. The behavioural recovery in both Mp and estrogen treated mice was investigated using the rotarod, foot printing and hanging tests. The recovery of dopamine neurons in the substantia nigra (SN) region was estimated by tyrosine hydroxylase (TH), immunostaining. Additionally inducible nitric oxide synthase (iNOS) and glial fibrillary acidic protein (GFAP) immunoreactivity was evaluated to assess the level of oxidative damage and glial activation respectively. The levels of dopamine and its metabolite in the nigrostriatal region were measured by HPLC. Mp treatment restored all the deficits induced by MPTP more effectively than estrogen. Mp treatment recovered the number of TH-positive cells in both the SN region and the striatum while reducing the expression of iNOS and GFAP in the SN. Treatment with Mp significantly increased the levels of dopamine, DOPAC and homovanillic acid compared to MPTP intoxicated mice. Notably, the effect of Mp was greater than that elicited by estrogen. Mp down regulates NO production, neuroinflammation and microglial activation and all of these actions contribute to Mp's neuroprotective activity. These results suggest that Mp can be an effective treatment for neurodegenerative diseases, especially PD by decreasing oxidative stress and possibly by implementing neuronal and glial cell crosstalk.

摘要

帕金森病(PD)是老龄化人群中最常见的神经退行性疾病之一。目前,许多研究正在进行,以寻找一种合适且有效的 PD 治疗方法,其中重点是使用草药植物。在阿育吠陀医学中,豆科植物豇豆属植物(Mucuna pruriens,Mp)被用作抗炎药物。在这项研究中,评估了 Mp 种子乙醇提取物在 1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)诱导的 PD 模型中的神经保护作用,并与雌激素(一种用于治疗 PD 的报告广泛的神经保护剂)进行了比较。24 只瑞士白化小鼠被随机分为四组:对照组、MPTP 组、MPTP+Mp 组和 MPTP+雌激素组。使用旋转棒、足迹和悬挂测试评估 Mp 和雌激素治疗小鼠的行为恢复情况。通过酪氨酸羟化酶(TH)免疫染色来估计黑质(SN)区域中多巴胺神经元的恢复情况。此外,评估诱导型一氧化氮合酶(iNOS)和胶质纤维酸性蛋白(GFAP)免疫反应性,以评估氧化损伤和神经胶质激活的程度。通过 HPLC 测量黑质纹状体区域中的多巴胺及其代谢物的水平。与雌激素相比,Mp 治疗更有效地恢复了 MPTP 诱导的所有缺陷。Mp 治疗恢复了 SN 区域和纹状体中 TH 阳性细胞的数量,同时降低了 SN 中 iNOS 和 GFAP 的表达。与 MPTP 中毒小鼠相比,Mp 治疗显著增加了多巴胺、DOPAC 和高香草酸的水平。值得注意的是,Mp 的作用大于雌激素。Mp 下调 NO 产生、神经炎症和小胶质细胞激活,所有这些作用都有助于 Mp 的神经保护活性。这些结果表明,Mp 可以通过降低氧化应激和可能通过实施神经元和神经胶质细胞的串扰,成为治疗神经退行性疾病,特别是 PD 的有效方法。

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